丙戊酸钠对博莱霉素致肺纤维化大鼠TNF—α表达的影响

Valproate modulated the expression of TNF-α in mice with bleomycin-induced pulmonary fibrosis

目的 探讨组蛋白脱乙酰基转移酶抑制剂丙戊酸钠在博莱霉素诱导肺纤维化大鼠的TNF-α表达的调节.方法 54只雄性SD大鼠随机分为控制对照组（CG）、肺纤维化模型组（MG）、丙戊酸钠干预组（VG）.MG组、VG组予以博莱霉素溶液按5mg/kg气管内注入建立大鼠肺纤维化模型,CG组予以等体积0.9% 氯化钠溶液注射.各组于造模后第7、14、28天分3批处死,观察肺组织大体及HE和Masson染色,Szapiel评分,进行大鼠肺组织羟脯氨酸（HYP）及肿瘤坏死因子-α（tumor necrosis factor-alpha,TNF-α）免疫组化检测.结果 与CG组相比,MG组14d和28d肺组织TNF-α及HYP含量明显增高（均P＜0.01）,VG组Szapiel评分、HYP受到明显抑制,TNF-α表达下降.结论 丙戊酸钠能抑制TNF-α表达,抑制BLM诱导的大鼠肺纤维化.

Objective To explore the effects of valproate, a histone deacetylase inhibitor （HDACI）on the expression of TNF- α in mice with bleomycin-induced（BLM ） pulmonary fibrosis（PF）. Methods Fifty-four SD mice were randomly divided into three groups （ 18 rats each group）,ie, a control group （CG）, a bleomycin-induced pulmonary fibrosis model group （MG） and a sodium valproate-treated group（VG）. Results It was founded that the hydroxyproline contents and Szapiel scores, the expression of TNF- α in MG and VG group were greatly increased, especially in MG group. However, the expression of TNF- α, the hydroxyproline contents and Szapiel scores in VG group were lower than those in MG group. Conclusion This study indicates that administration of valproate to the mice suffered from pulmonary fibrosis induced by bleomycin attenuates the fibrosis via inhibiting early inflammation.